Association of the COMT ‘Warrior’ and ‘Worrier’ Alleles with Academic Major
Rayne Nimz
Advisor: Dr. Aaron Davis, Department of Biology
Abstract
Discussion
The COMT gene is involved in the breakdown of the neurotransmitter dopamine
within the prefrontal cortex. Dopamine signaling plays a role in cognition and the
speed of dopamine breakdown has been shown to influence academic
performance by affecting stress level responses. The slow acting ‘worrier’ allele
of the COMT gene leads to prolonged dopamine signaling, which can lead to
increased anxiety and decreased performance in high-stress environments.
Despite the less favorable processing of stress, the ‘worrier’ allele leads to an
advantage in attention and memory tasks. Alternatively, the fast acting ‘warrior’
allele of the COMT gene results in the rapid breakdown of dopamine and is
more advantageous in stress processing, leading to increased performance in
high stress environments, and decreased performance in attention and memory
tasks. Academic achievement has been associated with the COMT genotype.
The goal of this study was to ascertain if a correlation existed between a COMT
allele and the major students elect to pursue while in college. 536 students from
the UWSP were genotyping for the COMT gene and assessed for association
significance. We identified one college (CLS-Hum) and one major (Psychology)
that are significantly correlated to the ‘worrier’ allele, and one major (Business
Administration) as significantly correlated to the ‘worrier’ allele.
0.8
Worrier (Met)
0.4
0.2
0
Combined
The COMT gene encodes for an enzyme that leads to the breakdown of
neurotransmitters in the brain, and is known to influence the stress response for
initiating the breakdown of dopamine within the prefrontal cortex. In addition to
stress processing, COMT also leads to differences in cognitive processing. A
single nucleotide polymorphism (SNP) within COMT (rs4680) has resulted in
two alleles that differ in the rate of dopamine breakdown. This mutation leads to
the incorporation of the amino acid Methionine at codon 158 (Met158) instead of
Valine (Val158). The Val158 allele is associated with high activity of COMT, and the
rapid removal of dopamine. The Met158 allele creates an enzyme that is less
efficient at dopamine breakdown. As the signaling of dopamine within the
prefrontal cortex affects cognition, memory, and the stress response pathway,
the Met158 allele leads to a slower degradation of dopamine resulting in higher
dopamine levels. High dopamine is associated increased attention and
increased academic cognition (1). However, high dopamine also leads to
activation of the stress response and leads to decreased performance in high
stress environments. The fast acting Val158 allele rapidly breaks down dopamine,
leading to a decrease in attention and academic cognition, but also increased
performance in high stress environments. Because of the high performance
when under stress, the Val158 is described as the ‘warrior’ allele and the Met158
allele is described as the ‘worrier’ allele due to the decreased performance in
high stress environments.
A 2009 study of Taiwanese students showed a poor overall exam performance
of the ’worrier’ allele, despite the advantage that it gives in memory and
academic cognition (2). The study concluded that the increased anxiety and
decreased emotional stability associated with higher levels of dopamine leads to
poor academic performance on high-pressure standardized exams. Within the
same environment, the ‘warrior’ allele performed better despite lower memory
and cognition, likely because of the greater performance under stress
associated with the allele.
We hypothesized that the selection of an academic major is influenced in part by
the COMT genotype. The advantage of increased memory and attention of the
‘worrier’ allele may predispose students towards majors in which memory and
attention ensures academic success. Likewise, the increased performance in
high stress environments of the ‘warrior’ allele may influence students towards
majors in which success is based on the ability to regularly perform in high
stress environments. We analyzed the COMT genotype of 536 students at the
University of Wisconsin-Stevens Point to determine if the genotype and
academic major correlate.
COMT Allele Summary
Warrior
Met158
Val158
A
G
Slower degradation of dopamine
Faster degradation of dopamine
Disadvantaged in memory and
attention
High performance under adverse
stimuli
CLS-Sci
CLS-Hum
CNR
COFAC
CPS
Summary of Study Participants
Average
Warrior Worrier
Sex
CLS-Sci CLS-Hum CNR CPS COFAC Undeclared Caucasian
Age
(Val)
(Met)
Total 304
20.1
102
39
60 269
32
34
92.4%
0.491
0.508
Male 117
20.0
48
16
39 109
6
18
94.0%
0.459
0.540
Female 187
20.1
54
23
21 160
26
16
91.4%
0.516
0.483
Allele Frequency of Majors
0.8
*
Warrior (Val)
0.6
0.4
0.2
0
Worrier
Low performance under adverse stimuli
Warrior (Val)
*
0.6
Background
Advantage of memory and attention
The COMT alleles are evenly distributed within a normal population, which was
observed among our combined group. A comparison of allele frequencies of
each colleges however revealed that the CLS–Hum significantly deviated from
the expected allele frequency, with a ’warrior’ allele frequency of 0.64. CNR
showed a strong shift toward a worrier allele, although was not considered
statistically significant.
In order to further extend our analysis, we analyzed the genotype of any major
from which we had 10 or more subjects. Seventeen majors were analyzed, and
the majors: English, Biochemistry, and Sociology/Social Work showed a strong
shift towards the ‘warrior’ allele. The majors: Communicative Disorders, Early
Childhood Education, Elementary Education, and Physical Education showed a
strong shift towards the worrier allele. Psychology was significantly different in
favor of the ‘warrior’ allele (P-value: 0.002). Of the 13 students with this major,
none were homozygous for the ‘worrier’ allele. Business Administration showed a
significant difference in favor of the ‘worrier’ allele (P-value: 0.026). Out of the 29
students only two of them were homozygous for the ‘warriors’ allele.
Different majors place different demands on students, and carriers of either allele
may be at an advantage or disadvantage depending on their COMT genotype.
Some majors may expose students to frequent high-pressure experiences, and
thereby selects for ‘warriors’. Other majors may require high attention and
cognitive focus and so ‘worriers’ are more likely to gravitate towards those
majors. Many factors contribute to what major a student pursues, and our data
suggests that the COMT genotype may contribute to that decision as we
demonstrated that there is a significant correlation between academic major and
the COMT allele. Future work will focus on the identified majors that are
significantly different, and increase the sample size to further understand how the
COMT allele contributes to a student’s decision to pursue a specific major. It
would also be of interest to determine if students who change majors tend to
leave majors where their COMT genotype is in the minority to one in which their
genotype is the majority.
Allele Frequency of Colleges
Worrier (Met)
*
Materials and Methods
Sample Collection
Surveys were given to all study participants regarding their age, ethnicity,
academic major, and athletic participation. These demographics are shown in
Table 2. 129 individual samples were collected from the athletes in baseball,
softball (women’s), tennis (women’s) volleyball, and track (men’s and women’s).
A total of 304 control samples were collected from students . All collection of
human samples was approved by the University of Wisconsin-Stevens Point
Institutional Review Board for the Protection of Human Subjects (submission #1415.055).
DNA Isolation
Buccal cells were extracted with 10ml of 0.9% saline solution. Cells were
centrifuged and pelleted cells were resuspended in 200µl TE buffer (SigmaAldrich, St. Louis, MO). DNA from athletes was extracted using the GeneJET
Genomic Purification Kit (Thermal Scientific, Waltham, MA). DNA of control
samples was extracted by adding 100µl of resuspended cells to 250µl 5% chelex
solution (Sigma-Aldrich) and incubated at 100˚C for ten minutes. Cell lysate was
centrifuged for three minutes at 14,000 rpm and kept at 4˚C until use.
Genotyping
Genotyping of the COMT allele was performed with allele-specific PCR. Primers
used were described by Ruiz-Sanz et al. (2). Each reaction contained four
primers: a control that produced a 686 bp product; a Val158 allele specific primer
that produced a 509 bp product; and a Met158 allele specific primer that produced
a 222 bp product. PCR reactions were carried out using GoTaq Mastermix
(Promega, Madison, WI) with 0.5 µM primer, 5% DMSO, and 20-200 ng DNA.
Following PCR, 20 µL PCR product was loaded into a 1% agarose gel and
imaged with the Gel Doc EZ Imager (Biorad, Hercules, CA).
Statistical Analysis
For statistical analysis the COMT genotype was coded by the number of Val158
alleles (Val158 homozygous: 2; heterozygous: 1; Met158 homozygous: 0). A t-test
compared each athlete group to the genotype of the control population. A p-value
of less than 0.05 was considered significant.
References
1.) Farrell, S., Tunbridge, E., Braeutigam, S., Harrison, P. 2011. Comt val(158)met
genotype determines the direction of cognitive effects produced by catechol-omethyltransferase inhibition. Biological Psychiatry. 77(3):304.
2) Ting-Kuang Y., Chun-Yen, C., Chung-Yi, H., Ting-Chi, Y., Ming-Yeh, L. 2009.
Association of catechol-o-methyltransferase (comt) polymorphism and
academic achievement in a chinese cohort. Brain and Cognition. 71:300-305.
Biology